腺病毒介导p16基因转移及诱导黑色素瘤细胞凋亡  

Apoptosis of human melanoma cell line WM 983A by p16 gene transduction

作　　者：程金科[1,2] 林晨[1,2] 邢嵘[1,2] 张雪艳[1,2] 牟巨伟[1,2] 王秀琴[1,2] 吴 

机构地区：[1]中国医学科学院中国协和医科大学肿瘤研究所肿瘤医院分子肿瘤学国家重点实验室 [2]大连医学院病理生理系

出　　处：《中华肿瘤杂志》1999年第2期89-92,共4页Chinese Journal of Oncology

基　　金：国家863高科技发展基金;世界实验室资助

摘　　要：目的进一步了解ｐ１６基因对肿瘤细胞的作用。方法通过腺病毒介导外源性ｐ１６基因转移到ｐ１６基因突变的人黑色素瘤细胞系ＷＭ９８３Ａ，对ｐ１６基因的表达、细胞生长的抑制与机制和对肿瘤模型的治疗效果进行分析。结果外源性ｐ１６基因在靶细胞高水平的表达显著地抑制了ＷＭ９８３Ａ的生长和集落形成，流式细胞仪检测显示细胞Ｇ１期阻滞并发生了凋亡。瘤内注射Ａｄｐ１６对裸鼠体内移植瘤有一定抑瘤作用。结论ｐ１６基因可能参与肿瘤细胞凋亡的诱导，使ｐ１６基因在肿瘤的基因治疗。Objective To further understand the mechanism of action of the tumor suppressor gene p16. Methods An adenoviral expression vector with full length cDNA of p16 gene insert was constructed (Ad p16) and transfected into WM 983A cells, the p16 gene of which was point mutated at codon 126. The effect of exogenous p16 gene on the growth of WM 983A cells was examined in vitro and in vivo. Results Expression of p16 gene in WM 983A cells was confirmed by Western blot. The in vitro growth of the Ad p16 transfected WM 983A cells was significantly inhibited (inhibition rate: 78%) as compared to mock (Ad LacZ) transfected WM 983A cells. Colony forming activity in vitro of the Ad p16 transfected WM 983A cells was completely inhibited. Morphologically, the Ad p16 transfected cells appeared apoptotic which was confirmed by the appearance of pre G1 on flow cytometry and DNA fragmentation. The growth of WM 983A xenografts in nude mice was retarded by intra tumoral injection of Ad p16. Conclusion p16 gene participates in the induction of cell apoptosis. It is promising to use it for gene therapy of cancer, especially when combined with other apopptosis inducing agents.

关 键 词：P16基因 基因转移 黑色素瘤 细胞凋亡 基因治疗 

分 类 号：R739.505[医药卫生—肿瘤] R730.5[医药卫生—临床医学]